Koonlawee Nademanee1, Gumpanart Veerakul2, Akihiko Nogami3, Qing Lou4, Mélèze Hocini5, Ruben Coronel6, Elijah R Behr7, Arthur Wilde8, Bastiaan J Boukens8, Michel Haissaguerre5. 1. Center of Excellence in Arrhythmia Research Chulalongkorn University, Bangkok, Thailand; Pacific Rim Electrophysiology Research Institute at Bumrungrad Hospital, Bangkok, Thailand. Electronic address: wee@pacificrimep.com. 2. Bhumibol Adulyadej RTAF Hospital, Bangkok, Thailand. 3. University of Tsukuba, Tsukuba, Japan. 4. CardioInsight Medtronic Inc., Minneapolis, Minnesota. 5. IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Pessac-Bordeaux, France. 6. IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Pessac-Bordeaux, France; Heart Centre, Department of Clinical and Experimental Cardiology, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands. 7. Cardiology Clinical Academic Group, Institute of Molecular and Clinical Sciences, St. George's, University of London, St. George's University Hospitals NHS Foundation Trust, London, United Kingdom. 8. Heart Centre, Department of Clinical and Experimental Cardiology, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands.
Abstract
BACKGROUND: The mechanisms by which sodium channel blockade and high-rate pacing modify electrogram (EGM) substrates of Brugada syndrome (BrS) have not been elucidated. OBJECTIVE: The purpose of this study was to determine the effect of ajmaline and high pacing rate on the BrS substrates. METHODS: Thirty-two patients with BrS (mean age 40 ± 12 years) and frequent ventricular fibrillation episodes underwent right ventricular outflow tract substrate electroanatomical and electrocardiographic imaging (ECGI) mapping before and after ajmaline administration and during high-rate atrial pacing. In 4 patients, epicardial mapping was performed using open thoracotomy with targeted biopsies. RESULTS: Ajmaline increased the activation time delay in the substrate (33%; P = .002), ST-segment elevation in the right precordial leads (74%; P < .0001), and the area of delayed activation (170%; P < .0001), coinciding with the increased substrate size (75%; P < .0001). High atrial pacing rate increased the abnormal EGM duration at the right ventricular outflow tract areas from 112 ± 48 to 143 ± 66 ms (P = .003) and produced intermittent conduction block and/or excitation failure at the substrate sites, especially after ajmaline administration. Biopsies from the 4 patients with thoracotomy showed epicardial fibrosis where EGMs were normal at baseline but became fractionated after ajmaline administration. In some areas, local activation was absent and unipolar EGMs had a monophasic morphology resembling the shape of the action potential. CONCLUSION: Sodium current reduction with ajmaline severely compromises impulse conduction at the BrS fibrotic substrates by producing fractionated EGMs, conduction block, or excitation failure, leading to the Brugada ECG pattern and favoring ventricular fibrillation genesis.
BACKGROUND: The mechanisms by which sodium channel blockade and high-rate pacing modify electrogram (EGM) substrates of Brugada syndrome (BrS) have not been elucidated. OBJECTIVE: The purpose of this study was to determine the effect of ajmaline and high pacing rate on the BrS substrates. METHODS: Thirty-two patients with BrS (mean age 40 ± 12 years) and frequent ventricular fibrillation episodes underwent right ventricular outflow tract substrate electroanatomical and electrocardiographic imaging (ECGI) mapping before and after ajmaline administration and during high-rate atrial pacing. In 4 patients, epicardial mapping was performed using open thoracotomy with targeted biopsies. RESULTS: Ajmaline increased the activation time delay in the substrate (33%; P = .002), ST-segment elevation in the right precordial leads (74%; P < .0001), and the area of delayed activation (170%; P < .0001), coinciding with the increased substrate size (75%; P < .0001). High atrial pacing rate increased the abnormal EGM duration at the right ventricular outflow tract areas from 112 ± 48 to 143 ± 66 ms (P = .003) and produced intermittent conduction block and/or excitation failure at the substrate sites, especially after ajmaline administration. Biopsies from the 4 patients with thoracotomy showed epicardial fibrosis where EGMs were normal at baseline but became fractionated after ajmaline administration. In some areas, local activation was absent and unipolar EGMs had a monophasic morphology resembling the shape of the action potential. CONCLUSION: Sodium current reduction with ajmaline severely compromises impulse conduction at the BrS fibrotic substrates by producing fractionated EGMs, conduction block, or excitation failure, leading to the Brugada ECG pattern and favoring ventricular fibrillation genesis.